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  Core facility  

[Background] [Summary] [Definition] [WholeSlideFFPE]

Medical and Scientific Background

Colorectal cancers (CRC) are the leading cancers in both genders. This cancer is of prognostic severity. The survival rate at 5 years is about 55%. The prognosis of this cancer has not been significantly improved. The therapeutic approach following the surgical removal of the tumor is being guided by the histopathological data of tumor invasion (UICC-TNM classification). Until now, this classification has been shown to be valuable in estimating the outcome of patients. Still, it provides limited information for prognosis since cancer outcome can significantly vary among patients within the same histological tumor stage. Nearly 30% of patients with localized colorectal cancer (stage II) will present a recurrence. The identification of new prognostic markers is a major issue for better therapeutic management of patients.

The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. Significant correlations were shown between the levels of immune cell infiltration in tumors and patient's clinical outcome. A strong lymphocytic infiltration associated with good clinical outcome has been reported in many different tumors, including colorectal cancers. Thus, high densities of T cells (CD3+), of cytotoxic T cells (CD8+), and of memory T cells (CD45RO+) were clearly associated with a longer disease-free (after surgical resection of the primary tumour) and/or overall survival. An immune-classification of tumors was proposed based on an immune score, performed by the quantification of two lymphocyte populations (CD3/CD8, or CD3/CD45RO, or CD8/CD45RO), both in the core of the tumor and the invasive margin of the tumor, to establish prognosis of clinical outcome in patients [11]. Importantly, this immune-classification has a prognostic value that may be superior to the AJCC/UICC TNM-classification.

Thus, a standard immune scoring system has now to be validated before incorporation into routine practice. The inherent complexity of quantitative immunohistochemistry underscore the urgent need to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings worldwide, the Society for Immunotherapy of Cancer (SITC), the European Academy of Tumor Immunology, the Cancer and Inflammation Program, the National Cancer Institute, National Institutes of Health, USA and "La Fondazione Melanoma" have jointly initiate a task force on Immunoscoring as a New Possible Approach for the Classification of Cancer. This worldwide effort was supported by the World Immunotherapy Council. An independent international consensus panel of histopathological laboratories with expertise in the field will evaluate the Immunoscore with a cross-laboratory assay validation for the development of an Immunoscore prognostic method.

Immunoscore summary

The outcome prediction in cancer is usually achieved by evaluating tissue samples obtained during surgical removal of the primary tumor focusing on their histopathological characteristics.

Tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N), and evidence for metastases (M). However, this classification provides limited prognostic information in estimating the outcome in cancer and does not predict response to therapy. It is recognized that cancer outcomes can vary significantly among patients within the same stage.

Recently, many reports suggest that cancer development is controlled by the host's immune system underlying the importance of including immunological biomarkers for the prediction of prognosis and response to therapy. Data collected from large cohorts of human cancers demonstrated that the immune-classification has a prognostic value that may be superior to the AJCC/UICC TNM-classification.

Thus, it is imperative to begin incorporating immune scoring as a prognostic factor and to introduce this parameter as a marker to classify cancers, as part of the routine diagnostic and prognostic assessment of tumors. At the same time, the inherent complexity of quantitative immunohistochemistry, in conjunction with variable assay protocols across laboratories, the different immune cell types analyzed, different region selection criteria, and variable ways to quantify immune infiltration underscore the urgent need to reach assay harmonization.

Immunoscore definition

Immunoscore using whole slide FFPE